Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key.

OBJECTIVE: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder. STUDY DESIGN: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients. RESULTS: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002). CONCLUSION: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.

Dimensional Reduction in Quantum Dipolar Antiferromagnets.

We report ac susceptibility, specific heat, and neutron scattering measurements on a dipolar-coupled antiferromagnet LiYbF_{4}. For the thermal transition, the order-parameter critical exponent is found to be 0.20(1) and the specific-heat critical exponent -0.25(1). The exponents agree with the 2D XY/h_{4} universality class despite the lack of apparent two-dimensionality in the structure. The order-parameter exponent for the quantum phase transitions is found to be 0.35(1) corresponding to (2+1)D. These results are in line with those found for LiErF_{4} which has the same crystal structure, but largely different T_{N}, crystal field environment and hyperfine interactions. Our results therefore experimentally establish that the dimensional reduction is universal to quantum dipolar antiferromagnets on a distorted diamond lattice.

Anatomy and radiology of the variations of aortic arch branches in 1,266 patients.

BACKGROUND: The most reliable data about arterial variations, which are very important in surgery and radiology, can be obtained from a large series of patients. MATERIALS AND METHODS: We examined angiographic and multislice computerised tomography (MSCT) images in a group of 1,265 patients and in 1 dissected specimen. RESULTS: While in 946 (74.72%) of the patients a normal vascular pattern (type I) was noticed, in the remaining 320 (25.28%) patients variations of the branches of the aortic arch were found, which were classified into types II through VIII and a few subtypes. Type II (2.84%) comprised a common origin of the left commoncarotid and subclavian arteries. Type III (15.56%) was related to an origin of the left subclavian artery from the brachiocephalic trunk. Type IV (0.55%) included the aortic origin of both common carotid and subclavian arteries, with the right subclavian artery having a retroesophageal course. Type V (0.24%) included the same 4 supra-aortic branches, which, however, arose from a double or a right--sided aortic arch. Type VI (3.63%) comprised the aortic origin of the left vertebral artery, type VII (0.24%) the same origin of the right vertebral artery, and type VIII(2.22%) the aortic origin of the thyroideaima artery. A corresponding embryological background and clinical implications of the described aberrant vessels were presented. CONCLUSIONS: In more than one quarter of the cases, the branching pattern of the examined arteries did not follow the classical pattern. Detailed knowledge of aortic branch variations is of great significance in anatomy, embryology, and clinical medicine, especially in radiology and thoracic surgery.

Clinical pattern of ocular toxoplasmosis treated in a referral centre in Serbia.

PURPOSE: To analyze the clinical pattern of ocular toxoplasmosis (OT) in a referral centre in Serbia. PATIENTS AND METHODS: The medical records of consecutive patients admitted for OT to the single referral centre for uveitis in Serbia between 2006 and 2010 were retrospectively analyzed. OT was diagnosed on the basis of typical fundus lesions and positive serology for Toxoplasma. RESULTS: In a total of 457 uveitis patients, OT was the third leading cause, with 59 patients (12.9%). Most OT cases (73%) were monocular. An active primary retinal lesion was observed in 36% and recurrent OT in 64% patients. Localization of lesions was central/paracentral (44%), juxtapapillar (27%), peripheral (19%), and multifocal (10%). Other ocular manifestations of inflammation included vitritis (44%), anterior uveitis (19%), and retinal vasculitis (10%). Complications included choroidal neovascularization in two and exudative retinal detachment with cataract, glaucoma, and cystoid macular oedema in one patient each. The detection of Toxoplasma-specific IgM antibodies in a single patient indicates a low rate of OT concomitant with acute infection. After treatment, the mean best-corrected visual acuity (BCVA) increased significantly. However, 14 (24%) patients ended up legally blind in the affected eye, of which 2 (3%) with bilateral blindness, all with a very poor BCVA (0.047 ± 0.055) at presentation. Visual impairment and treatment outcome were both associated with central localization of lesions (P<0.0001 and P=0.006, respectively). CONCLUSION: OT is a significant cause of posterior uveitis in Serbia. Patients should be aware of the recurring nature of OT and react immediately if symptoms occur.

Comparison of liquid chromatography with fluorescence detection to liquid chromatography-mass spectrometry for the determination of fluoxetine and norfluoxetine in human plasma.

A comparison study on fluoxetine (FL) and norfluoxetine (NORFL) quantitation in human plasma was carried out between the recently developed liquid chromatographic method with fluorescence detection (LC-FLD) and an earlier established liquid chromatography-mass spectrometry (LC-MS) laboratory procedure. Comparative method evaluation was based on the analysis of plasma samples obtained from Parkinsonian patients receiving 20mg of FL per day. The LC-FLD method involves a two-step liquid extraction procedure without any derivatization, followed by direct chromatography on a Zorbax C8 reversed-phase column. The analytical results are discussed in terms of the method validation and the corresponding experimental protocol (r>/=0.998; CV<9%; LOQ 20 microg/l). There was good correlation between FL, as well as NORFL, plasma levels as determined by the LC-MS and LC-FLD techniques (r=0.9597, N=16 and r=0.9852, N=14 for FL and NORFL, respectively). The results confirm that direct FL/NORFL fluorimetric determination is acceptable for routine use in pharmacokinetic and clinical studies.

Liquid chromatographic-mass spectrometric method for the determination of fluoxetine and norfluoxetine in human plasma: application to clinical study.

A selective, sensitive, simple, and rapid method for the simultaneous determination of fluoxetine (FL) and norfluoxetine (nor-FL) was developed and validated, and further applied to analyze plasma samples obtained from FL-treated patients with Parkinson disease (n = 18). After one step liquid-liquid extraction with ethyl acetate, plasma samples were chromatographed on a C8 column. The mobile phase was acetate buffer and acetonitrile (40:60 v/v). Determination of FL and nor-FL was performed with MS detection in selective ion monitoring (SIM) mode, so the other components did not interfere with this assay. FL, nor-FL and flumazenil as internal standard were eluted in 6 min. Recoveries ranged from 89.7 to 96.6% and from 80.2 to 85.3% for FL and nor-FL, respectively. The limit of quantitation under described conditions was 2.5 microg/l for FL and 10 microg/l for nor-FL. The method was found to be reproducible with coefficient of variation less than 9%. The parameters of the method were found to be acceptable to enable its routine use for clinical studies. The method was employed to analyze the Parkinsonian patients' plasma samples. A great deviation in plasma concentrations of FL and nor-FL found among 18 studied patients indicates high pharmacokinetic variability of the drug. Obtained results also indicate absence of the influence of Parkinson disease on the drug disposition.

Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose during and after moderate physical exercise in patients with type 2 diabetes.

OBJECTIVE: To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3 h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5 min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min, separated by 30 min rest, starting 3 h after a 339 kcal breakfast. RESULTS: The 2-h postprandial PG was significantly lower with Mix25 ((mean +/- SEM) 10.5 +/- 0.4 mmol/l vs 11.6 +/- 0.4 mmol/l; p = 0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6 +/- 0.29 mmol/l vs -4.7 +/- 0.31 mmol/l; p = 0.001). The maximum decrease in PG over 6 h, after exercise onset, was significantly less with Mix25 (-4.3 +/- 0.4 mmol/l vs -5.9 +/- 0.4 mmol/l; p < 0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7 +/- 0.2 episodes/30 d vs 1.2 +/- 0.3 episodes/30 d; p = 0.042). CONCLUSIONS: Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.

Helicobacter pylori infection in patients with Brunner's gland adenoma.

Histopathologic and clinical data strongly suggest a causal relation between Helicobacter pylori infection and gastritis, peptic ulcer disease, or both. However, little has been written about the potential association between H. pylori infection and Brunner's gland adenoma. Therefore, we carried out a prospective study to determine the presence of H. pylori infection among patients with Brunner's gland adenoma. From November 1996 till October 1999, 19100 patients who had undergone upper gastrointestinal endoscopy at two clinical centers in Zagreb, Croatia, were candidates for participation in the study. Brunner's gland adenoma was diagnosed on the basis of histologic samples taken from the polyp (four patients) or after the entire polyp was made available upon endoscopic removal (three patients). When all endoscopic examinations had been performed, biopsy samples were taken from the antrum and body of the stomach, so that gastritis could be classified and H. pylori determined by histology. Biopsy samples were also taken from the duodenal bulb to verify duodenitis. Two other samples were taken from the antrum for rapid urease test. The patients were considered positive for H. pylori when both histology and rapid urease test were positive. Brunner's gland adenoma was diagnosed in seven patients (five women and two men; median age, 49 yrs). Five (71%) patients with diagnosed Brunner's gland adenoma had concurrent H. pylori infection. Duodenitis associated with gastric metaplasia was observed in six patients. Complete eradication of H. pylori was achieved in only two patients. Symptoms disappeared or markedly diminished in all patients with significant improvement during therapy or immediately upon endoscopic removal of the polyp. Although limited by a very small number of patients, our results suggest that concurrent H. pylori infection is very common in patients with Brunner's gland adenoma. However, the role of H. pylori infection in the pathogenesis and development of Brunner's gland hyperplasia remains unclear.

The effect of eradicating Helicobacter pylori infection on the course of adenomatous and hyperplastic gastric polyps.

OBJECTIVE: Histopathological and clinical data strongly suggest that Helicobacter pylori is the cause of chronic gastritis and peptic ulceration. However, little has been written about the potential causal relation of H. pylori infection to hyperplastic and adenomatous gastric polyps. We therefore carried out a prospective study to determine the effect of eradicating H. pylori infection on the course of hyperplastic and adenomatous gastric polyps. METHODS: From November 1996 to December 1997, 6700 patients who had undergone upper gastrointestinal endoscopy at the two centres in Zagreb, Croatia, were candidates for participation in the study. Hyperplastic and adenomatous polyps were diagnosed on a basis of at least three histological samples taken from the polyp. In seven patients endoscopy had to be repeated because forceps biopsy sampling either provided inadequate tissue for correct histological diagnosis, or accurate characterization of gastric polyp histology was not possible. Upon completion of all endoscopic examinations before and after treatment, biopsy samples were taken from the antrum (two) and the body of the stomach (two) so that gastritis could be graded and classified, and the presence of H. pylori sought by histology. Two other samples were taken from the antrum for a rapid urease test. Follow-up examinations were performed by using endoscopy. Control endoscopy was performed at least 4 weeks after the treatment of H. pylori infection had been completed, and then every 3-4 months. The follow-up ranged from 4 to 17 months, with a median of 14 months. The treatment of H. pylori infection consisted of a 1-week course of either omeprazole (20 mg twice daily) or pantoprazole 40 mg twice daily), and a 1-week course of amoxicillin 2g twice daily) and metronidazole (400 mg three times daily), and clarithromycin (500 mg twice daily). Eradication of H. pylori infection was assessed by repeated histology and rapid urease test. RESULTS: Twenty-one patients (nine women, 12 men; median age 52 years) with histologically proven hyperplastic gastric polyps, and seven patients (two women, five men; median age, 67 years) with adenomatous gastric polyps were included in the study. Among 21 patients with hyperplastic gastric polyps, 16 patients (76%) were positive for H. pylori infection. Only two patients (29%) with adenomatous gastric polyps were positive for the infection. Complete eradication of H. pylori was initially achieved in all patients positive for H. pylori. Total regression of the gastric polyps was observed only among the patients with hyperplastic gastric polyps in whom H. pylori had been eradicated. Complete regression of the hyperplastic gastric polyps was observed in seven of the 16 evaluable patients (44%; 95% CI, 19-68%) after H. pylori eradication. The endoscopic snare polypectomy was carried out in nine patients with hyperplastic polyps and two patients with adenomatous gastric polyps in whom regression of the polyps was not observed after H. pylori eradication, as well as in five patients with hyperplastic and four with adenomatous gastric polyps who were negative for H. pylori. Exploratory laparotomy and gastrotomy with polyps excision were carried out in one patient with multiple adenomatous gastric polyps. In only one patient who was not positive for H. pylori recurrence of hyperplastic gastric polyp was recorded during follow-up, and no re-infection with H. pylori has been detected. CONCLUSIONS: Our results suggest that the development of hyperplastic gastric polyps may be directly related to chronic active gastritis and concomitant H. pylori infection. Cure of H. pylori infection associated with hyperplastic gastric polyps resulted in complete polyp regression in more than 40% of patients. Therefore, for patients with hyperplastic gastric polyps and concurrent H. pylori infection an antibiotic treatment designed to eradicate H. pylori appears to be recommended before further therapeutic options are consi

Medical treatment of gastroesophageal reflux disease.

Medical therapy for reflux esophagitis is designed to provide symptom relief and esophageal healing, and to prevent complications. Life-style modifications serve as an adjunct to drug therapy. Histamine-H2-receptor antagonists and prokinetic agents promote symptom relief and esophageal healing in mild esophagitis, but are less effective in the treatment of moderate to severe esophagitis. For patients with moderate to severe esophagitis, rapid symptom relief and esophageal healing have been achieved with proton pump inhibitors. These patients usually require maintenance therapy with proton pump inhibitors.

[Complications after primary surgical management of war injuries of the colon and rectum]. / Komplikacije posle primarnog hirurskog zbrinjavanja ratnih povreda kolona i rektuma.

War injuries of colon and rectum are real challenge for war surgeons. The aim of the study was to point out the necessity of war surgical doctrine application, considering the risk factors in the choice of primary surgical procedure and surgeon's experience in managing this kind of injuries. Postoperative complications and indications for reoperations in 216 wounded after primary surgical management of colonic and rectal war injuries in the period 1991-1995 were retrospectively analyzed. A total of 183 wounded (84.7%) were primarily surgically managed in war hospitals. Combined injuries of colon and/or rectum or more than 2 abdominal organs were found in 197 wounded (91.2%), and 29.1% of wounded were also with the combined extra-abdominal injuries. Postoperative complications were observed in 58 wounded (26.8%) and were associated with the injury and primary management of colon and rectum, with septic complications in 87.9% of cases. Reoperation was performed in 44 wounded (75.8%) and the most frequent indications, such as diffuse peritonitis and stercoral fistula, were the sequlae of dehiscence of suture or anastomosis, overlooked lesions and secondary perforations (blast) of colon or rectum. Principle of complete diversion of stool/intestinal content was used in reoperation. Mortality rate in reoperated group was 20.4% (9 wounded). Cause of death was diffuse peritonitis followed by consecutive sepsis and MOFS. The significance of surgical war doctrine and risk factors in the choice of primary surgical procedures were emphasized.

Ulcerative colitis in Zagreb, Yugoslavia: incidence and prevalence 1980-1989.

We present a ten-year incidence of ulcerative colitis in Zagreb, Yugoslavia. The study included both outpatients and inpatients regardless of the extent and severity of the disease. The mean annual incidence rate was 1.5 per 100,000 inhabitants for the period of 1 January 1980 through 31 December 1989. There was no increase in the incidence of ulcerative colitis during the study period. A prevalence rate estimate of 21.4 per 100,000 inhabitants was based on July 1985 official estimated population. The results confirm the low frequency of ulcerative colitis in central Europe.

Epidemiology of Crohn's disease in Zagreb, Yugoslavia: a ten-year prospective study.

A ten-year prospective study of Crohn's disease was carried out in Zagreb, Yugoslavia. It included both inpatients and outpatients regardless of the extent and severity of the disease. The mean annual incidence rate was 0.7 per 100,000 between 1 January 1980 and 31 December 1989. There was no increase in the incidence of Crohn's disease during the study period. The prevalence of Crohn's disease was 8.3 per 100,000 on 31 December 1989. The results confirm the low frequency of Crohn's disease in central and southern Europe.